The Association between Epidermal Growth Factor Receptor (EGFR) Gene Polymorphisms and Lung Cancer Risk

Abstract

Lung cancer is the leading cause of cancer death globally. The epidermal growth factor receptor (EGFR) plays an important role in cell proliferation and signaling. In this study, we examined the association between EGFR gene polymorphisms and lung cancer risk among the Jordanian population. A total of 129 patients with primary lung cancer and 129 matched healthy controls were recruited into this study. EGFR rs712829, rs712830, rs2072454, and rs11543848 single nucleotide polymorphisms (SNPs) were genotyped to test for their association with lung cancer risk. A significant association was observed between the rs712829 SNP and lung cancer risk (p < 0.05) where the GG + GT genotypes were higher in lung cancer patients when compared to controls. In addition, no association was detected between rs712830, rs2072454, and rs11543848 SNPs and lung cancer risk. When patients were stratified according to the lung cancer type, a significant association was detected between both rs712829 and rs2072454 and adenocarcinoma lung cancer (p < 0.05). Haplotype analysis of all four SNPs showed a significant association between the TCCG haplotype and both lung cancer and the adenocarcinoma subtype (p < 0.001). In conclusion, EGFR rs712829, rs2072454 SNPs, and TCCG haplotypes are associated with a risk of lung cancer among Jordanians. Since genetic associations are affected by the genetic background of populations, more studies in other Arab populations are required to confirm the present findings. Support or Funding Information The study was supported by funding provided by the Ministry of Higher Education—Scientific Research Fund (SRF) grant number JUST‐1‐2016. Genotypes/Allele Pattern Patients Controls p‐Value For rs712829 GG 12 (28%) 29 (22%) 0.020 TT 4 (9%) 35 (27%) GT 27 (63%) 65 (50%) For rs712830 CC 41 (95%) 121 (94%) 0.670 CA 2 (5%) 8 (6%) For rs2072454 CC 6 (14%) 15 (12%) 0.027 TT 26 (60%) 57 (44%) CT 11 (26%) 57 (44%) For rs11543848 AA 8 (19%) 26 (20%) 0.073 GG 2 (5%) 18 (14%) GA 33 (77%) 85 (66%)Note: Rs29: rs712829, Rs30: rs712830, Rs54: rs2072454 and Rs48: rs11543848. Haplotype Rs29 Rs30 Rs54 Rs48 Frequency Odd Ratio (95% CI) p‐Value 1 T C T A 0.2118 1.00 — 2 G C T A 0.1748 1.00 (0.31–3.24) 1 3 G C T G 0.1552 0.93 (0.34–2.55) 0.9 4 T C T G 0.1228 1.38 (0.32–5.96) 0.66 5 G C C G 0.0953 1.08 (0.31–3.67) 0.91 6 T C C A 0.0794 1.46 (0.33–6.43) 0.62 7 G C C A 0.0681 0.69 (0.15–3.15) 0.63 8 T C C G 0.0629 168,507 (168,498–168,517) <0.001 9 G A T G 0.0156 0.71 (0.08–6.39) 0.76Note: Rs29: rs712829, Rs30: rs712830, Rs54: rs2072454 and Rs48: rs11543848.

The Polymorphisms of Epidermal Growth Factor-driven Signaling and Cancer Pathogenesis

“…Some of these polymorphisms, such as rs4444903, were widely studied and meta-analyses were conducted to increase the strength of the results. The findings can be explained by the functional importance of these SNPs, many of them leading to an increase in the pathway activity, and, in the end, promoting the progression of the malignancy [21,39,40]. [23][24][25][26][27][28], glioma [29][30][31][32][33][34], lung cancer [38][39][40][41][42], breast cancer [36,37], cervical cancer [45], and head and neck cancer [46].…”

“…Sudan Journal of Medical Sciences Monica Dugăeșescu et al microsatellite sequence in the first intron have regulatory functions regarding transcription [29]. -191C/A SNP results in an increased production of EGFR and it occurs at the binding site of the promoter region with a transcription factor [39,40]. While -216 G/T genotype was not significantly associated with glioma, -191 C/A SNP was associated with higher risk of developing glioma.…”

“…Rs712829 EGFR polymorphism (GG+GT), rs2072454, -191C/A (rs712830), rs6965469, rs763317, and TCCG haplotype of rs712829, rs712830, rs2072454, rs11543848 were associated with lung cancer [39][40][41].…”

Instance-based error correction for short reads of disease-associated genes

“…It is vital to provide error-free reads related to these specific genes [ 20 ] for the precise detection of SNVs and accurate discovery of SNPs. As another example in the mutation and protein research area, error correction is important because one or two DNA base mutations in the coding region of a gene may lead to functionally different amino acids [ 21 – 23 ], and more likely when the open reading frame mechanism is considered. These mutations are called point mutations, and more than 31,000 such mutations in the human genome are associated with genetic diseases [ 24 ].…”

Association between EGFR Gene Mutation and Antioxidant Gene Polymorphism of Non-Small-Cell Lung Cancer

“…It plays important roles in regulating various physiological functions, including cell proliferation and migration [ 3 ]. Activating mutations in EGFR gene are observed frequently in non-small-cell lung carcinoma patients [ 4 ], and EGFR gene polymorphisms are associated with the risk of lung cancer [ 5 ]. It is well-documented that the most common EGFR mutations including exon 19 deletions and L858R mutations strongly predict the sensitivity of lung cancer patients to tyrosine kinase inhibitor treatments [ 6 ].…”